Position dependence of the 13C chemical shifts of α-helical model peptides. Fingerprint of the 20 naturally occurring amino acids

VILA, JORGE A.; BALDONI, HÉCTOR A.; SCHERAGA, HAROLD A.

PROTEIN SCIENCE

JOHN WILEY & SONS INC

Año: 2004 vol. 13 p. 2939 - 2948

0961-8368

The position dependence of the 13C chemical shifts was investigated at the density functional level for α-helical model peptides represented by the sequence Ac-(Ala)i-X-(Ala)j-NH 2, where X represents any of the 20 naturally occurring amino acids, with 0 ≤ i ≤ 8 and i + j = 8. Adoption of the locally dense basis approach for the quantum chemical calculations enabled us to reduce the length of the chemical-shift calculations while maintaining good accuracy of the results. For the 20 naturally occurring amino acids in α-helices, there is (1) significant variability of the computed 13C shielding as a function of both the guest residue (X) and the position along the sequence; for example, at the N terminus, the 13Cα and 13C β shieldings exhibit a uniform pattern of variation with respect to both the central or the C-terminal positions; (2) good agreement between computed and observed 13Cα and 13C β chemical shifts in the interior of the helix, with correlation coefficients of 0.98 and 0.99, respectively; for 13C α chemical shifts, computed in the middle of the helix, only five residues, namely Asn, Asp, Ser, Thr, and Leu, exhibit chemical shifts beyond the observed standard deviation; and (3) better agreement for four of these residues (Asn, Asp, Ser, and Thr) only for the computed values of the 13Cα chemical shifts at the N terminus. The results indicate that 13Cα, but not 13C β, chemical shifts are sensitive enough to reflect the propensities of some amino acids for specific positions within an α-helix, relative to the N and C termini of peptides and proteins.